Preparation and biodistribution of [125I]IBZP: a potential CNS D-1 dopamine receptor imaging agent.

Carrier free [125I]IBZP, R-(+)-8-[125I] iodo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol), was prepared from the corresponding uniodinated compound by an oxidative iodination reaction with chloramine-T and sodium [125I]iodide. After purification by column chromatography the desired uptake was obtained with a high purity (greater than 95%). The agent showed good localization in brain after i.v. injection in rats, with an uptake of 2.7, 1.2 and 0.8% dose/organ at 2, 15 and 30 min post injection, respectively. The regional distribution in rat brain, as measured by in vivo autoradiography, displayed a high uptake in the caudate putamen, accumbens nucleus and substantia nigra, regions known to have a high concentration D-1 dopamine receptors. The uptake ratio of striatum/cerebellum increased with time; at 30 s and 2 h after injection the ratio was 1.1 and 5.3, respectively. The specific uptake in the D-1 dopamine receptor regions can be blocked by pretreatment with SCH-23390, a selective D-1 dopamine receptor antagonist (SCH-23390). The corresponding iodine-123 (t1/2 = 13 h, gamma energy 159 keV) labeled agent may be suitable for SPECT imaging of CNS D-1 dopamine receptors.

Preparation and biodistribution of [125I]IBZM: a potential CNS D-2 dopamine receptor imaging agent.

A new CNS D-2 dopamine receptor imaging agent [125I]IBZM, (S)-3-[125I]-iodo-N-[(1-ethyl-2-pyrrolidinyl)] methyl-2-hydroxy-6-methoxybenzamide, was prepared by either an exchange reaction or by the chloramine-T method. After an i.v. injection, the agent easily passed through the blood-brain barrier and localized in the rat brain. At 2, 15, 30 and 60 min after the injection, the brain uptake was 2.9, 2.3, 1.8 and 0.7% dose/organ, respectively. Regional uptake ratio of striatum/cerebellum (target to nontarget ratio) increased from 1.4 at 30 s to 10.3 at 2 h after the i.v. injection. Digital autoradiography of rat brain sections showed high regional uptake in the caudate putamen and accumbens nucleus, areas known to have a high concentration of the D-2 dopamine receptor. The specific uptake at the D-2 dopamine receptor site was blocked by pretreatment with spiperone, a selective D-2 antagonist. When labeled with 123I (t1/2 = 13 h, 159 keV), [123I]IBZM may be useful for imaging the CNS D-2 dopamine receptor.